Genomic Analyses of Non-Coding RNAs Overlapping Transposable Elements and Its Implication to Human Diseases

Abstract

It is estimated that up to 80% of the human genome is transcribed into RNA molecules but less than 2% of the genome encodes the proteins, and the rest of the RNA transcripts that are not translated into protein are called non-coding RNAs (ncRNAs). Many studies have revealed that ncRNAs have biochemical activities as epigenetic regulators at the post-transcriptional level. Growing evidence has demonstrated that transposable elements (TEs) contribute to a large percentage of ncRNAs' transcription. The TEs inserted into certain parts of the genome can act as alternative promoters, enhancers, and insulators, and the accumulation of TEs increases genetic diversity in the human genome. The TEs can also generate microRNAs, so-called miRNA-derived from transposable elements (MDTEs), and are also implicated in disease progression, such as infectious diseases and cancer. Here, we analyzed the origin of ncRNAs and reviewed the published literature on MDTEs related to disease progression.

Keywords: MDTE; disease; long non-coding RNA; non-coding RNA; transposable element.

Figure 1

Percentage and composition of lncRNA transcripts overlapping TE sequences. (A) The percentage of TE subclasses produced by each chromosome; (B) The number of TE superfamilies overlapping with lncRNA transcripts from each TE subclasses: LTR, SINE, LINE, and DNA transposon.

Figure 2

The schematic diagram of miRNA biogenesis via three independent pathways. TE, transposable element; m⁷G, 7-methylguanosine; DGCR8, DiGeorge syndrome critical region 8; TRBP, transactivation response element RNA-binding protein; RISC, RNA-Induced Silencing Complex; AGO, Argonaute.

Figure 3

Percentage and composition of MDTEs. (A) The proportion of MDTEs in total miRNA and the distribution of TE subclasses from which miRNAs are derived; (B) The number of TE superfamilies that generate miRNAs from each TE subclasses, DNA transposon, LINE, SINE, and LTR.

Figure 4

Chromosome ideogram shows the MDTEs in relation to (A) infectious diseases or (B) cancers. Each diagram indicates the chromosomal location of these MDTEs.

Figure 5

Volcanoplot of differentially expressed miRNAs in the tissue of 9 types of cancer obtained from TCGA database. Only those MDTEs with the significant expression alteration that satisfy the condition (p  <  0.05 and |log₂FC| ≥ 1.0) are presented. Red dots represent significantly upregulated miRNAs, and greens for downregulated miRNAs.